Annexins comprise a multigene family of calcium- and phospholipid-binding proteins. They are structurally divided into a conserved core domain and a flexible N-terminal domain. The core domain contains four (in the case of annexin A6, eight) repeats, which fold into five α-helices (named A through E) each. The overall shape of the annexin core is a curved disk with the calcium binding sites located on the concave face and the N-terminal domain on the convex face. Annexins contain three different calcium binding sites: type II, type III, and AB′ sites. Type II and AB′ sites are found in the loops between the A and the B helix of each repeat. The coordination sphere for the calcium ion in the type II site generally comprises three backbone carbonyl oxygens, the side chain of an acidic residue 39 residues downstream of the AB loop, and two water molecules. The AB′ site is formed by one backbone carbonyl oxygen, one nearby acidic residue, and four to five water molecules. The calcium ion in the type III binding site, which is usually located in the loop between the D and E helix, is coordinated by two backbone carbonyl oxygens, one acidic residue nearby, and three to four water molecules. In comparison to EF hand calcium-binding proteins, the affinity for calcium ions of annexins is rather low, which might be due to the large number of water molecules involved in the coordination of the calcium ions. In this review, we will give an overview on the structure and function of several mammalian annexins. We will also discuss in detail the coordination of calcium ions in the different types of calcium binding sites found in annexins.